Insulin resistance predicts sustained virological response to treatment of chronic hepatitis C independently of the IL28b rs12979860 polymorphism

Summary Background Insulin resistance has been strongly associated with the attainment of sustained viral response (SVR) in hepatitis C patients. Aim To determine, in a cohort of Spanish patients with chronic hepatitis C treated with peginterferon plus ribavirin (P+R), whether insulin resistance predicts SVR independently of interleukin‐28B rs12979860 polymorphism. Methods Insulin resistance was measured as [HOMA‐IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and histological fibrosis using Scheuer score were also measured. Binary logistic regression analysis was used for statistical purposes. Results In a cohort of 240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load (≥800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R, 126 (53%) reached SVR. HOMA‐IR index (HOMA 2: 42%; P = 0.001 and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were significantly associated with SVR. In multivariable logistic regression analysis in the overall cohort, variables independently associated were: viral genotype OR: 0.29 (95% CI: 0.11–0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22–2.16), P = 0.001; HOMA‐IR OR: 1.22 (95% CI: 1.02–1.47), P = 0.03; and IL28B genotype OR: 2.43 (95% CI: 1.45–4.07), P = 0.001. The analyses also showed that degree of steatosis, HOMA‐IR >2, mild fibrosis and IL28B CC genotype were significantly related to SVR in patients infected with HCV genotypes 1&4, but not in those with genotypes 2&3. No differences were seen in glucose, insulin level or HOMA‐IR index segregated according to IL28B genotypes. Conclusion Our results suggest that insulin resistance, fibrosis stage and IL28B polymorphisms were independent variables associated with sustained viral response.